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HIV-1 activates the host complement system, which results in opsonization of virus by inactivated complement fragments, for example, iC3b. We investigated antiviral and inflammatory responses induced in human iDCs after exposure to free HIV-1 (F-HIV), complement-opsonized HIV-1 (C-HIV), and complement and Ab\u2013opsonized HIV-1 (CI-HIV). F-HIV gave rise to a significantly higher expression of antiviral factors such as IFN-\u03b2, myxovirus resistance protein A, and IFN-stimulated genes, compared with C-HIV and CI-HIV. Additionally, F-HIV induced inflammatory factors such as IL-1\u03b2, IL-6, and TNF-\u03b1, whereas these responses were weakened or absent after C-HIV or CI-HIV exposure. The responses induced by F-HIV were TLR8-dependent with subsequent activation of IFN regulatory factor 1, p38, ERK, PI3K, and NF-\u03baB pathways, whereas these responses were not induced by C-HIV, which instead induced activation of IFN regulatory factor 3 and Lyn. This modulation of TLR8 signaling was mediated by complement receptor 3 and led to enhanced infection. The impact that viral hijacking of the complement system has on iDC function could be an important immune evasion mechanism used by HIV-1 to establish infection in the host.<\/jats:p>","DOI":"10.4049\/jimmunol.1401781","type":"journal-article","created":{"date-parts":[[2014,9,25]],"date-time":"2014-09-25T05:44:34Z","timestamp":1411623874000},"page":"4590-4601","source":"Crossref","is-referenced-by-count":38,"title":["Complement Opsonization of HIV-1 Results in Decreased Antiviral and Inflammatory Responses in Immature Dendritic Cells via CR3"],"prefix":"10.1093","volume":"193","author":[{"given":"Rada","family":"Elleg\u00e5rd","sequence":"first","affiliation":[{"name":"Division of Molecular Virology, Department of Clinical and Experimental Medicine, Link\u00f6ping University , 581 85 Link\u00f6ping ,","place":["Sweden"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisa","family":"Crisci","sequence":"additional","affiliation":[{"name":"Division of Molecular Virology, Department of Clinical and Experimental Medicine, Link\u00f6ping University , 581 85 Link\u00f6ping ,","place":["Sweden"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adam","family":"Burgener","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, University of Manitoba , Winnipeg, Manitoba R3E 0J9 ,","place":["Canada"]},{"name":"National Microbiology Laboratory, Public Health Agency of Canada , Winnipeg, Manitoba R3E 3R2 ,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher","family":"Sj\u00f6wall","sequence":"additional","affiliation":[{"name":"Division of Rheumatology\/Autoimmunity and Immune Regulation Unit, Department of Clinical and Experimental Medicine, Link\u00f6ping University , 581 85 Link\u00f6ping ,","place":["Sweden"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenzie","family":"Birse","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, University of Manitoba , Winnipeg, Manitoba R3E 0J9 ,","place":["Canada"]},{"name":"National Microbiology Laboratory, Public Health Agency of Canada , Winnipeg, Manitoba R3E 3R2 ,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Garrett","family":"Westmacott","sequence":"additional","affiliation":[{"name":"National Microbiology Laboratory, Public Health Agency of Canada , Winnipeg, Manitoba R3E 3R2 ,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jorma","family":"Hinkula","sequence":"additional","affiliation":[{"name":"Division of Molecular Virology, Department of Clinical and Experimental Medicine, Link\u00f6ping University , 581 85 Link\u00f6ping ,","place":["Sweden"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey D","family":"Lifson","sequence":"additional","affiliation":[{"name":"Leidos Biomedical Research, Inc., Frederick National Laboratory , Frederick, MD 21702"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marie","family":"Larsson","sequence":"additional","affiliation":[{"name":"Division of Molecular Virology, Department of Clinical and Experimental Medicine, Link\u00f6ping University , 581 85 Link\u00f6ping ,","place":["Sweden"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2014,11,1]]},"reference":[{"key":"2025030707432066900_r1","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1038\/nm1643","article-title":"Lasker Basic Medical Research Award. 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